A general aim of this research proposal is to obtain information on mechanisms of genetic variation and their rates of occurrence in somatic cells of humans. HL-A alloantigens will be used to select out genetic variants from cultured human fibroblasts and lymphoid cells. The variants will then be characterized in terms of their alloantigens and certain enzymatic markers. The genetic relationship between immunoglobulin and alloantigen expression will be studied by characterizing the immunoglobulins produced by sublines variant at the HL-A locus. The regulation of mitochondrial enzyme synthesis in human cells by oxygen will be studied by combined immunological and biochemical approach.